Under certain conditions non-permissive for growth, such as high density or serum deprivation, human or rodent fibroblasts enter a stationary phase, during which DNA synthesis and cell division all but cease. When these resting cultures are stimulated to proliferate (for instance, by serum), the cells enter, after a lag period, DNA synthesis and subsequently mitosis. We intend to continue our studies aimed at elucidating the intranuclear mechanisms controlling the flow of cells from the Go to the S phase of the cell cycle, as well as the maintenance of transformation in culture. For this purpose, we shall use cell cycle-specific temperature-sensitive mutants, i.e., mammalian cells that grow normally at the permissive temperature (usually, 33 degrees or 34 degrees centigrade) but arrest at a specific point of the cell cycle at the non-permissive temperature (39.5 degrees or 40 degrees centigrade.) We shall also use virally-transformed cells and study, by somatic cell hybridization, how they can regulate the cell cycle flow in G1-arrested temperature-sensitive mutants.